Ionic channels in nerve and muscle membranes of frogs will be investigated under voltage clamp conditions to understand how they open and close and how ions cross them when they are open. The channels to be studied are the K channel, the Na channel, and the cholinergic endplate channel. The specific projects include simultaneous measurements of intracellular pH as channel gating is being modified by amino-acid specific reagents, study of gating kinetics in Na channels modified by purified natural toxins, measurement of K channel gating steps by fluctuation analysis, and analysis of the elementary steps of permeation for organic cations crossing endplate channels.